We propose to continue our long-standing novel methodological developments in dietary pattern analyses. Specifically, this study builds upon and extends our recent earlier work on dietary pattern factors and coronary heart disease (CHD), and presents a novel, comprehensive way to study and objectively test the exciting new theory of fatty acid lipophilicity and membrane fluidity in the development of CHD. Toward this end, we will create the Lipophilic Index (LI) of fatty acids, indexed on fatty acid melting points to reflect fat fluidity. We will test the hypothesis that this index is associated with risk of CHD by analyzing nutritional biochemical data from two large ongoing prospective cohort studies -- the Nurses'Health Study (NHS) and Health Professionals'Follow-up Study (HPFS). Our first specific aim is to conduct a nested case-control study of plasma and erythrocyte membrane Lipophilic Index (LI) and risk of CHD. This study will include 620 incident cases of CHD and 1,240 matched controls from the NHS and HPFS. The LI is computed by summing the product of relative density of each fatty acid (a proportion of total fatty acids) in plasma or erythrocyte membrane and the respective melting point of each fatty acid. Plasma and erythrocyte fatty acids have already been measured in 170 CHD cases and 340 healthy controls in NHS. In this 2-year grant, we will measure plasma and erythrocyte fatty acid profile 450 CHD cases and 900 controls in HPFS. Because these cases and controls have already been selected in an ongoing study, we will be able to prepare blood and erythrocyte samples for laboratory analysis in a timely fashion. The laboratory analysis is expected to be completed by September, 2010. In addition, we will analyze relations between dietary, plasma, and erythrocyte indices of fat lipophilicity and major etiological biomarkers of CHD (inflammation, insulin resistance, lipids, and endothelial dysfunction) in the controls in both NHS and HPFS. These markers have already been measured in both NHS and HPFS through other grants. This study proposes a novel approach to examining the role of dietary fatty acids in the development of CHD. The LI presents a unifying paradigm to studying fatty acids and CHD risk, potentially contributing to a better understanding of the relationship between diet and CHD.